Identification of an amino acid transporter associated with the cystinuria-related type II membrane glycoprotein

We identified an amino acid transporter that is associated with the cystinu ria-related type II membrane glycoprotein, rBAT (related to b(0,+) amino ac id transporter). The transporter designated BAT1 (b(0,+)'-type amino acid t ransporter 1) from rat kidney was found to be structurally related to recen tly identified amino acid transporters for system L, system y(+)L, and syst em x-C, which are linked, via a disulfide bond, to the other type II membra ne glycoprotein, 4F2hc (4F2 heavy chain). In the nonreducing condition, a 1 25-kDa band, which seems to correspond to the heterodimeric complex of BAT1 and rBAT, was detected in rat kidney with anti-BAT1 antibody. The band was shifted to 41 kDa in the reducing condition, confirming that BAT1 and rBAT are linked via a disulfide bond. The BAT1 and rBAT proteins were shown to be colocalized in the apical membrane of the renal proximal tubules where m assive cystine transport had been proposed. When expressed in COS-7 cells w ith rBAT, but not with 4F2hc, BAT1 exhibited a Na+-independent transport of cystine as well as basic and neutral amino acids with the properties of sy stem b(0,+). The results from the present investigation were used to establ ish a family of amino acid transporters associated with type II membrane gl ycoproteins.